Bariatric surgery is the most effective weight loss option for persons with extreme obesity (i.e., body mass index = 40 kg/m2). Roux-en-Y gastric bypass (RYGB) and laparoscopic adjustable gastric banding (LAGB) are the most common bariatric procedures, and they induce long-term reductions of ~25% and ~15% of initial weight, respectively. Anatomical differences resulting from the two procedures are associated with postoperative differences in endocrine functioning. In particular, the orexigenic hormone, ghrelin, is generally suppressed in RYGB and increased in LAGB patients. Furthermore, postprandial increases in the satiety factors, glucagon-like peptide 1 (GLP-1) and peptide YY (PYY3-36), are significantly increased after RYGB, compared with LAGB. Each of these appetite-regulating hormones has been found to act in brain regions related to both the homeostatic and hedonic control of food intake. A separate literature has examined neural activation in feeding centers, as measured with functional magnetic resonance imaging (fMRI) and positron emitted tomography (PET), in response to food cues. Most of these studies have compared responses to images of high-calorie vs. low-calorie foods or non-food items. Some have further compared responses in lean vs. obese individuals. Generally, high-calorie food images stimulate activation in the prefrontal cortex, mesolimbic dopamine system (e.g., ventral-tegmental area and nucleus accumbens), and other limbic areas (e.g., orbitofrontal cortex, amygdala, insula, and cingulate cortex). Furthermore, responses are greater in obese vs. lean individuals. Fewer studies have examined neural response to meal consumption;those investigations have found that many of the same regions are activated by nutrient ingestion. The proposed research is a prospective observational study that seeks to integrate two areas of inquiry: 1) endocrine effects of bariatric surgery;and 2) neural response to food cues and feeding. Patients who undergo RYGB or LAGB, and matched obese controls who do not seek weight loss, will complete assessment visits at 0, 6, and 18 months, which include: 1) a fMRI scan while viewing high- and low-calorie food images in the fasted state;2) a perfusion MRI scan to measure cerebral blood flow in the fasted state;3) fasting blood draw;4) consumption of a liquid test meal;5) serial perfusion MRI scans to assess the effects of the meal;and 5) serial blood draws to assess postprandial changes in ghrelin, GLP-1, and PYY3-36. Comparisons of changes among the three groups at 6-months and 18-months follow-up will comprise our primary analyses. The primary hypotheses are that following surgery: 1) fMRI response to high-calorie food images will be reduced in RYGB vs. LAGB patients and controls;2) RYGB patients will show larger increases in postprandial GLP-1 and PYY3-36 (accompanied with a blunted postprandial ghrelin response) than will LAGB patients and controls;and 3) RYGB patients will demonstrate a greater postprandial increase in resting brain activity in homeostatic and hedonic feeding areas than will LAGB and control participants. PUBLIC HEALTH RELEVANCE: The proposed research is an 18-month prospective observational study of extremely obese patients who seek laparoscopic adjustable gastric banding (LAGB) or roux-en-Y gastric bypass (RYGB) surgery. Using functional and perfusion magnetic resonance imaging, we will assess changes in neural response to food cues and meal ingestion 6 and 18 months after surgery. Changes in the two surgical approaches will be compared with each other and with those in a group of extremely obese individuals who do not seek weight loss. In addition, we will serially measure postprandial changes in appetite-regulating hormones and examine the relationships between neural and endocrine response to food consumption.